{"title":"糖基化对开发用于医疗用途的特定细胞因子及其衍生物的影响。","authors":"","doi":"10.1016/j.biotechadv.2024.108467","DOIUrl":null,"url":null,"abstract":"<div><div>Cytokines are important regulators of immune responses, making them attractive targets for autoimmune diseases and cancer therapeutics. Yet, the significance of cytokine glycosylation remains underestimated. Many cytokines carry <em>N</em>- and <em>O</em>-glycans and some even undergo <em>C</em>-mannosylation. Recombinant cytokines produced in heterologous host cells may lack glycans or exhibit a different glycosylation pattern such as varying levels of galactosylation, sialylation, fucosylation or xylose addition compared to their human counterparts, potentially impacting critical immune interactions.</div><div>We focused on cytokines that are currently utilized or designed in advanced therapeutic formats, including immunocytokines, fusokines, engager cytokines, and genetically engineered ‘supercytokines.’ Despite the innovative designs of these cytokine derivatives, their glycosylation patterns have not been extensively studied. By examining the glycosylation of the human native cytokines, G-CSF and GM-CSF, interferons β and γ, TNF-α and interleukins-2, −3 -4, −6, −7, −9, −12, −13, −15, −17A, −21, and − 22, we aim to assess its potential impact on their therapeutic derivatives. Understanding the glycosylation of the native cytokines could provide critical insights into the safety, efficacy, and functionality of these next-generation cytokine therapies, affecting factors such as stability, bioactivity, antigenicity, and half-life. This knowledge can guide the choice of optimal expression hosts for production and advance the development of effective cytokine-based therapeutics and synthetic immunology drugs.</div></div>","PeriodicalId":8946,"journal":{"name":"Biotechnology advances","volume":null,"pages":null},"PeriodicalIF":12.1000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Implications of glycosylation for the development of selected cytokines and their derivatives for medical use\",\"authors\":\"\",\"doi\":\"10.1016/j.biotechadv.2024.108467\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Cytokines are important regulators of immune responses, making them attractive targets for autoimmune diseases and cancer therapeutics. Yet, the significance of cytokine glycosylation remains underestimated. Many cytokines carry <em>N</em>- and <em>O</em>-glycans and some even undergo <em>C</em>-mannosylation. Recombinant cytokines produced in heterologous host cells may lack glycans or exhibit a different glycosylation pattern such as varying levels of galactosylation, sialylation, fucosylation or xylose addition compared to their human counterparts, potentially impacting critical immune interactions.</div><div>We focused on cytokines that are currently utilized or designed in advanced therapeutic formats, including immunocytokines, fusokines, engager cytokines, and genetically engineered ‘supercytokines.’ Despite the innovative designs of these cytokine derivatives, their glycosylation patterns have not been extensively studied. By examining the glycosylation of the human native cytokines, G-CSF and GM-CSF, interferons β and γ, TNF-α and interleukins-2, −3 -4, −6, −7, −9, −12, −13, −15, −17A, −21, and − 22, we aim to assess its potential impact on their therapeutic derivatives. Understanding the glycosylation of the native cytokines could provide critical insights into the safety, efficacy, and functionality of these next-generation cytokine therapies, affecting factors such as stability, bioactivity, antigenicity, and half-life. This knowledge can guide the choice of optimal expression hosts for production and advance the development of effective cytokine-based therapeutics and synthetic immunology drugs.</div></div>\",\"PeriodicalId\":8946,\"journal\":{\"name\":\"Biotechnology advances\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.1000,\"publicationDate\":\"2024-10-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biotechnology advances\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0734975024001617\",\"RegionNum\":1,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biotechnology advances","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0734975024001617","RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Implications of glycosylation for the development of selected cytokines and their derivatives for medical use
Cytokines are important regulators of immune responses, making them attractive targets for autoimmune diseases and cancer therapeutics. Yet, the significance of cytokine glycosylation remains underestimated. Many cytokines carry N- and O-glycans and some even undergo C-mannosylation. Recombinant cytokines produced in heterologous host cells may lack glycans or exhibit a different glycosylation pattern such as varying levels of galactosylation, sialylation, fucosylation or xylose addition compared to their human counterparts, potentially impacting critical immune interactions.
We focused on cytokines that are currently utilized or designed in advanced therapeutic formats, including immunocytokines, fusokines, engager cytokines, and genetically engineered ‘supercytokines.’ Despite the innovative designs of these cytokine derivatives, their glycosylation patterns have not been extensively studied. By examining the glycosylation of the human native cytokines, G-CSF and GM-CSF, interferons β and γ, TNF-α and interleukins-2, −3 -4, −6, −7, −9, −12, −13, −15, −17A, −21, and − 22, we aim to assess its potential impact on their therapeutic derivatives. Understanding the glycosylation of the native cytokines could provide critical insights into the safety, efficacy, and functionality of these next-generation cytokine therapies, affecting factors such as stability, bioactivity, antigenicity, and half-life. This knowledge can guide the choice of optimal expression hosts for production and advance the development of effective cytokine-based therapeutics and synthetic immunology drugs.
期刊介绍:
Biotechnology Advances is a comprehensive review journal that covers all aspects of the multidisciplinary field of biotechnology. The journal focuses on biotechnology principles and their applications in various industries, agriculture, medicine, environmental concerns, and regulatory issues. It publishes authoritative articles that highlight current developments and future trends in the field of biotechnology. The journal invites submissions of manuscripts that are relevant and appropriate. It targets a wide audience, including scientists, engineers, students, instructors, researchers, practitioners, managers, governments, and other stakeholders in the field. Additionally, special issues are published based on selected presentations from recent relevant conferences in collaboration with the organizations hosting those conferences.